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Original Investigation
May 22/29, 2018

Effect of Vitamin D Supplementation on Recurrent Wheezing in Black Infants Who Were Born PretermThe D-Wheeze Randomized Clinical Trial

Author Affiliations
  • 1Case Western Reserve University, Cleveland, Ohio
  • 2University Hospitals Cleveland Medical Center, Cleveland, Ohio
  • 3Shawn Jenkins Children’s Hospital, Medical University of South Carolina, Charleston
  • 4The Children’s Hospital at Montefiore, Albert Einstein College of Medicine, Bronx, New York
  • 5MetroHealth Medical Center, Cleveland, Ohio
JAMA. 2018;319(20):2086-2094. doi:10.1001/jama.2018.5729
Key Points

Question  Does sustained vitamin D supplementation until 6 months of age affect recurrent wheezing in black infants born preterm?

Findings  In this randomized clinical trial of 300 infants, sustained supplementation with 400 IU/d of vitamin D until 6 months of age, compared with a diet-limited approach, resulted in a likelihood of recurrent wheezing at 12 months of 31.1% vs 41.8%, respectively, a statistically significant difference.

Meaning  Among black infants born preterm, sustained supplementation with vitamin D, compared with diet-limited supplementation, resulted in a reduced risk of recurrent wheeze by 12 months’ adjusted age.

Abstract

Importance  Black infants born preterm face high rates of recurrent wheezing throughout infancy. Vitamin D supplementation has the potential to positively or negatively affect wheezing through modulation of the pulmonary and immune systems.

Objective  To assess the effectiveness of 2 vitamin D dosing strategies in preventing recurrent wheezing.

Design, Setting, and Participants  A randomized clinical trial enrolled 300 black infants born at 28 to 36 weeks’ gestation between January 2013 and January 2016 at 4 sites in the United States, and followed them up through March 2017. Randomization was stratified by site and maternal milk exposure.

Interventions  Patients were enrolled prior to discharge from the neonatal intensive care unit or newborn nursery and received open-label multivitamin until they were consuming 200 IU/d of cholecalciferol from formula or fortifier added to human milk, after which they received either 400 IU/d of cholecalciferol until 6 months of age adjusted for prematurity (sustained supplementation) or placebo (diet-limited supplementation). One-hundred fifty three infants were randomized to the sustained group, and 147 were randomized to the diet-limited group.

Main Outcomes and Measures  Recurrent wheezing by 12 months’ adjusted age was the primary outcome.

Results  Among 300 patients who were randomized (mean gestational age, 33 weeks; median birth weight, 1.9 kg), 277 (92.3%) completed the trial. Recurrent wheezing was experienced by 31.1% of infants in the sustained supplementation group and 41.8% of infants in the diet-limited supplementation group (difference, −10.7% [95% CI, −27.4% to −2.9%]; relative risk, 0.66 [95% CI, 0.47 to 0.94]). Upper and lower respiratory tract infections were among the most commonly reported adverse events. Upper respiratory infections were experienced by 84 of 153 infants (54.9%) in the sustained group and 83 of 147 infants (56.5%) in the diet-limited group (difference, −1.6% [95% CI, −17.1% to 7.0%]). Lower respiratory infections were experienced by 33 of 153 infants (21.6%) in the sustained group and 37 of 147 infants (25.2%) in the diet-limited group (difference, −3.6% [95% CI, −16.4% to 4.4%]).

Conclusions and Relevance  Among black infants born preterm, sustained supplementation with vitamin D, compared with diet-limited supplementation, resulted in a reduced risk of recurrent wheezing by 12 months’ adjusted age. Future research is needed to better understand the mechanisms and longer-term effects of vitamin D supplementation on wheezing in children born preterm.

Trial Registration  ClinicalTrials.gov Identifier: NCT01601847

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